Individuals with fewer nigrostriatal dopamine neurons appear to have increased vulnerability to insults and neuropathological processes that lead to Parkinson's disease. We have shown that young adult rats raised from conception on a diet low in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) have decreased brain levels of the n-3 PUFA docosahexaenoic acid (DHA) and decreased numbers of nigrostriatal dopamine neurons. The objective of this application is to identify mechanisms by which an n-3 PUFA-deficient diet leads to decreased numbers of nigrostriatal dopamine neurons, and if this decrease in dopaminergic cell number leads to increased sensitivity to dopaminergic neurotoxins. The hypothesis is that decreased brain DHA content leads to decreased survival of dopamine neurons under normal and pathological conditions. The Specific Aims are to identify candidate mechanisms by which low dietary n-3 PUFA content results in decreased numbers of nigrostriatal dopamine neurons and determine the effects of low dietary n-3 PUFA content on neurotoxic lesion of nigrostriatal dopamine neurons. Expected outcomes from these studies include novel means for preventing and/or slowing progression of Parkinson's disease, as well as increased understanding of the role of phospholipid long chain PUFA composition in neuronal function. Findings may also clarify the underlying pathology of Parkinson's disease, and form a basis for future clinical studies. PUBLIC HEALTH RELEVANCE: Parkinson's disease is a debilitating progressive neurodegenerative disorder affecting 0.1-0.2% of the general population and 2% of people over 65 years of age. The objective of this application is to identify potential factors contributing to the development of Parkinson's disease using a rat model.